PB2163: BORTEZOMIB - CYCLOPHOSPHAMIDE – DEXAMETHASONE (VCD) REGIMEN IN NEWLY DIAGNOSED MULTIPLE MYELOMA (NDMM) - EXPERIENCE FROM A RESOURCE CONSTRAINT SETTING IN SOUTH INDIA
Authors: Rahmathullah Sulaimankutty Nameera, Raghuveer Prabhu
Journal: HemaSphere (2023)

Topic: 14. Myeloma and other monoclonal gammopathies - Clinical Background: With novel drugs, esp IMiDs and proteosome inhibitors, deep response rates and prolonged survival is achievable in patients with multiple myeloma. The availability of generic bortezomib has made the wider use of this molecule feasible and reduced the financial burden on MM patients in lower/middle income countries(LMIC) Aims: We did a retrospective analysis of our data of newly diagnosed NDMM patients treated with VCd induction therapy. We studied the response after 6 cycles of VCd and the associated toxicities Methods: Patients with NDMM on induction with VCd from April 2019 to July 2022 at a single center in South India were included. Response rates after the 2nd and the 6th cycles were studied. Major dose limiting toxicities were analyzed Results: 26 patients were included in the study (16 males; 10 females). Median age was 64 years (range 44 to 79). 13 (50 %) were >65 years. Performance status was ≥ 2 in 13/26 (50 %). 17/26 (65.4 %) patients were ISS III. Median follow up was 17.5 months (IQR 8 – 29). 24/26 patients had anemia. Renal dysfunction present in 15/26 patients. 16/26 and 6/26 had skeletal lesions and hypercalcemia respectively. Cytogenetic studies were done only in 7 patients due to resource constraints- 3 had del 13q abnormalities. Patients received weekly VCd with bortezomib dose of 1.5 mg/m2 given subcutaneously. IV route was preferred in patients with renal dysfunction in the initial cycles (cycles 1, 2). Cyclophosphamide and dexamethasone were given by oral route in standard doses. 1 patient lost to follow up. Of the rest 25 patients, 1 discontinued VCd due to bilateral optic atrophy which occurred during the 1st cycle. Of the 24 patients who completed 2 cycles, the ORR at 2 cycles was 20/24(83.3 %) with CR 4/24(16.7 %), VGPR 8/24(33.3 %) and PR 8/24(33.3 %). 4/24 (16.7 %) had stable disease with 2 cycles. 3 patients who had stable disease with 2 cycles of VCd switched to lenalidomide based regimen - VRd. 1 patient switched to Len-dex regimen due to grade 2 peripheral neuropathy after 2 cycles. 1 patient preferred maintenance therapy after 4 cycles.19 patients completed 6 cycles VCd - ORR 17/19 (89.5 %) with CR 9/19 (47.4 %), VGPR 7/19 (36.8 %), PR 1/19 (5.3 %). 2/19 (10.5 %) had stable disease. None had progressive disease during the 6 cycles of VCd. Minimal residual disease was not monitored as it was not widely available. In an intention to treat (ITT) analysis, the ORR was 65.4 % (17/26) with VCd after 6 cycles, with CR of 34.6 % (9/26), VGPR 26.9 % (7/26) and PR 5.3 % (1/26). There were no deaths during the 6 cycles of VCd. The major toxicity was ≥ grade 2 peripheral neuropathy (PN) in 11/25 (44 %). Notably 1 patient had bilateral optic atrophy. 2/25 discontinued due to neuropathy. Bortezomib related chalazia of eyelids were seen in 2 patients. Cytopenias were seen in only 2 patients with one having grade 3 neutropenia - none required colony stimulating factors. 2 patients had grade 2 infections (cellulitis & otitis) and one had grade 3 covid pneumonia. VCd was well tolerated (only 2 patients discontinued due to neuropathy). 8/25 patients (32 %) required bortezomib dose reduction - six were above 68 years Summary/Conclusion: VCd is an effective regimen for NDMM patients with early deep response rates, which is important to achieve prolonged PFS. In our study, with ITT analysis, 65.4 % achieved ≥ VGPR. With generic bortezomib, the regimen can be delivered for € 60 per cycle. This is especially important in LMICs like India, where the out of pocket expenditure for healthcare is around 60 %. Neuropathy is the major adverse effect, which needs to be closely monitored and can be countered with timely dose modifications, making VCd a feasible regimen even for elderly Keywords: Bortezomib, Multiple myeloma, Induction chemotherapy, Clinical outcome